Autoradiography of antidepressant binding sites in the human brain: localization using [3h]imipramine and [3h]paroxetine

Cortés, Roser; Soriano, Eduardo; Pazos, Ángel; Probst, A.; Palacios, J.M.

doi:10.1016/0306-4522(88)90282-5

Cited by 202 publications

(108 citation statements)

References 67 publications

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“…Therefore, using the radiotracer [ 123 I]b-CIT, it will be very difficult to distinguish between SERT and DAT binding in the cortical areas and this would only be possible when selective blockers for DAT and norepinephrine transporter are used simultaneously. As expected, we found much lower [ 123 I]b-CIT binding ratios in the cortex than in the midbrain and (hypo)thalamus, because the SERT concentration is much lower in the cerebral cortex than in the midbrain or diencephalon (Cortés et al, 1988;Bäck-ström et al, 1989). These low binding densities and corresponding low signal-to-noise ratios cause poor visualization and delineation by which placement of ROI templates in the cerebral cortex is hampered.…”

Section: Discussionsupporting

confidence: 82%

“…Since the cerebellum is not devoid of SERTs (Cortés et al, 1988;Bäckström et al, 1989), this might be explained by an MDMA-induced decreased availability of SERTs in the cerebellum. Both SSRI and MDMA pretreatment could be used to evaluate the specificity of radiotracer binding to SERTs.…”

Section: Discussionmentioning

confidence: 99%

“…One study validated the use of in vivo [ 123 I]b-CIT SPECT in detecting MDMA-induced serotonergic neurotoxicity in SERT-rich brain areas in a monkey (Reneman et al, 2002). Second, previous SSRI displacement studies did not validate the in vivo [ 123 I]b-CIT binding to SERTs in cortical regions, probably because the interpretation in these areas is hampered by low SERT and DAT densities (Cortés et al, 1988;Bäckström et al, 1989;Heinz and Jones, 2000). Since studies in non-human primates showed long-term and possible irreversible damage of serotonergic axons in the cerebral cortex induced by MDMA (Hatzidimitriou et al, 1999), assessment of SERT density in the cerebral cortex is especially important for studying the neurotoxic effects of ecstasy.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram

Win

Habraken

Reneman

et al. 2005

Neuropsychopharmacol

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Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram

Win

Habraken

Reneman

et al. 2005

Neuropsychopharmacol

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“…locus coerulus, thalamic and hypothalamic nuclei and bed nucleus of the strai terminalis (Fig.2, top row), areas known to have high densities of NET sites [31]. A medium level of labeling was observed in the median raphe, and dentate gyrus.…”

Section: Biological Evaluationsmentioning

confidence: 94%

(R)-N-Methyl-3-(3-125I-pyridin-2-yloxy)-3-phenylpropan-1-amine: a novel probe for norepinephrine transporters

Balagopal¹,

Kung²,

Lieberman³

et al. 2008

Nuclear Medicine and Biology

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Alterations in the serotonin and norepinephrine neuronal functions have been observed in patients with major depression. Several antidepressants bind to both serotonin transporters (SERT) and norepinephrine transporters (NET). The ability to image NET in the human brain would be a useful step toward understanding how alterations in NET relate to disease. In this study, we report the synthesis and characterization of a new series of derivatives of iodo-nisoxetine (INXT), a known radioiodinated probe. The most promising, (R)-N-methyl-3-(3-iodopyridin-2-yloxy)-3-phenylpropylamine (PYINXT) 9, displayed a high and saturable binding to NET with a K d value of 0.53 ± 0.03 nM. Biodistribution studies of [ 125 I]PYINXT in rats showed moderate initial brain uptake (0.54 %dose/organ at 2 min) with a relatively fast washout from the brain (0.16 %dose/organ at 2 hr) as compared to [ 125 I]INXT, 7. The hypothalamus (a NET rich region) to striatum (a region devoid of NET) ratio was found to be 2.14 at 4 hr post i.v. injection. The preliminary results suggest that this improved iodinated ligand, when labeled with 123 I, may be useful for mapping NET binding sites with SPECT in the living human brain.

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“…Rat brain sections showed intense labeling in several regions [46], i.e. lateral hypothalamic area (LH), dorsomedial hypothalamic nucleus (DM), interpeduncular nucleus (IP), thalamus nuclei (ThN), dorsal raphe (DR), medial raphe (MR), superior colliculus (SC), locus coeruleus (LC), sustantia nigra (SN), globus pallidus (GP), areas known to have high densities of SERT sites [47]. Lower, but detectable, labeling was also found in the frontal cortex, caudate putamen, ventral pallidum and hippocampus, areas containing a significantly lower number of SERT sites.…”

Section: Biodistribution In Ratsmentioning

confidence: 99%

5-Chloro-2-(2′-((dimethylamino)methyl)-4′-iodophenylthio)benzenamine: a new serotonin transporter ligand

Oya

Choi

Kung

et al. 2007

Nuclear Medicine and Biology

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Two novel ligands with a 4′-substitution on the phenyl ring B of biphenylthiol: 5-chloro-2-(2′-((dimethylamino)methyl)-4′-iodophenylthio)benzenamine, 7, and 2-(2′-((dimethylamino) methyl)-4′-methoxyphenylthio)-5-iodobenzenamine, 8, were prepared and tested as potential serotonin transporter (SERT) imaging agents. The new ligands displayed extremely high binding affinities to SERT (K i = 0.22 ± 0.09 and 0.11 ± 0.04 nM, respectively), with very low binding affinities to dopamine and norepinephrine transporters (K i > 1, 000 nM). The corresponding [ 125 I]7 and [ 125 I] 8 were successfully prepared from the tri-n-butyltin derivatives. They showed good brain uptakes and prolonged retention after iv injection in rats (brain uptake was 1.77 and 0.98 %dose/g for [ 125 I] 7 and 0.92 and 0.29 %dose/g for [ 125 I]8 at 2 and 120 minutes, respectively). Significantly, [ 125 I]7 showed excellent uptake and prolonged retention in the hypothalamus, where the SERT concentration is the highest. The hypothalamus/cerebellum ratios (target to background ratios) were 4.24, 7.10, 8.24 and 12.6 at 2, 4, 6 and 12 hours, respectively. The hypothalamus/cerebellum ratios for [ 125 I]8 were 3.97, 5.57 and 5.06 at 1, 2 and 4 hours, respectively. Adding the 4′-iodo-group to the phenyl ring B of 7 appeared to reduce the rate of clearance from the brain, and the kinetics favored uptake and retention in the hypothalamus. The localization of [ 125 I]7 in the hypothalamus region in the brain of rats could be blocked by pretreatment with (+)McN5652, escitalopram and ADAM (2), all selective serotonin transporter ligands (at 2 mg/Kg dose, iv, 5 min pretreatment). Ex vivo autoradiograms of rat brain sections (at 4 hr after iv injection of [ 125 I]7) showed intense labeling in regions of the brain known to have high SERT density. The excellent selective uptake and retention in the hypothalamus region suggests that [ 123 I]7 is a potential lead compound for developing new imaging agents targeting SERT binding sites with single photon emission computed tomography (SPECT).

show abstract

Autoradiography of antidepressant binding sites in the human brain: localization using [3h]imipramine and [3h]paroxetine

Cited by 202 publications

References 67 publications

Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram

Validation of [123I]β-CIT SPECT to Assess Serotonin Transporters In Vivo in Humans: a Double-Blind, Placebo-Controlled, Crossover Study with the Selective Serotonin Reuptake Inhibitor Citalopram

(R)-N-Methyl-3-(3-125I-pyridin-2-yloxy)-3-phenylpropan-1-amine: a novel probe for norepinephrine transporters

5-Chloro-2-(2′-((dimethylamino)methyl)-4′-iodophenylthio)benzenamine: a new serotonin transporter ligand

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